Palaeolithic cave art in Borneo.

Figurative cave paintings from the Indonesian island of Sulawesi date to at least 35,000 years ago (ka) and hand-stencil art from the same region has a minimum date of 40 ka1. Here we show that similar rock art was created during essentially the same time period on the adjacent island of Borneo. Uranium-series analysis of calcium carbonate deposits that overlie a large reddish-orange figurative painting of an animal at Lubang Jeriji Saléh-a limestone cave in East Kalimantan, Indonesian Borneo-yielded a minimum date of 40 ka, which to our knowledge is currently the oldest date for figurative artwork from anywhere in the world. In addition, two reddish-orange-coloured hand stencils from the same site each yielded a minimum uranium-series date of 37.2 ka, and a third hand stencil of the same hue has a maximum date of 51.8 ka. We also obtained uranium-series determinations for cave art motifs from Lubang Jeriji Saléh and three other East Kalimantan karst caves, which enable us to constrain the chronology of a distinct younger phase of Pleistocene rock art production in this region. Dark-purple hand stencils, some of which are decorated with intricate motifs, date to about 21-20 ka and a rare Pleistocene depiction of a human figure-also coloured dark purple-has a minimum date of 13.6 ka. Our findings show that cave painting appeared in eastern Borneo between 52 and 40 ka and that a new style of parietal art arose during the Last Glacial Maximum. It is now evident that a major Palaeolithic cave art province existed in the eastern extremity of continental Eurasia and in adjacent Wallacea from at least 40 ka until the Last Glacial Maximum, which has implications for understanding how early rock art traditions emerged, developed and spread in Pleistocene Southeast Asia and further afield.

An early modern human presence in Sumatra 73,000-63,000 years ago.

Genetic evidence for anatomically modern humans (AMH) out of Africa before 75 thousand years ago (ka) and in island southeast Asia (ISEA) before 60 ka (93-61 ka) predates accepted archaeological records of occupation in the region. Claims that AMH arrived in ISEA before 60 ka (ref. 4) have been supported only by equivocal or non-skeletal evidence. AMH evidence from this period is rare and lacks robust chronologies owing to a lack of direct dating applications, poor preservation and/or excavation strategies and questionable taxonomic identifications. Lida Ajer is a Sumatran Pleistocene cave with a rich rainforest fauna associated with fossil human teeth. The importance of the site is unclear owing to unsupported taxonomic identification of these fossils and uncertainties regarding the age of the deposit, therefore it is rarely considered in models of human dispersal. Here we reinvestigate Lida Ajer to identify the teeth confidently and establish a robust chronology using an integrated dating approach. Using enamel-dentine junction morphology, enamel thickness and comparative morphology, we show that the teeth are unequivocally AMH. Luminescence and uranium-series techniques applied to bone-bearing sediments and speleothems, and coupled uranium-series and electron spin resonance dating of mammalian teeth, place modern humans in Sumatra between 73 and 63 ka. This age is consistent with biostratigraphic estimations, palaeoclimate and sea-level reconstructions, and genetic evidence for a pre-60 ka arrival of AMH into ISEA. Lida Ajer represents, to our knowledge, the earliest evidence of rainforest occupation by AMH, and underscores the importance of reassessing the timing and environmental context of the dispersal of modern humans out of Africa.

[Significance of IgA isotype of anti-v-raf murine sarcoma viral oncogene homologue B1 antibody in rheumatoid arthritis].

OBJECTIVE: To detect serum IgA isotype of anti-v-raf murine sarcoma viral oncogene homologue B1 (BRAF) antibody levels in the rheumatoid arthritis (RA) patients in order to investigate their clinical significance in RA. METHODS: Serum samples were obtained from 61 RA patients, 21 osteoarthritis (OA) patients, 16 systemic lupus erythematosus (SLE) patients, 16 gout patients, 16 Sjögren's syndrome (SS) patients and 22 healthy controls. IgA isotype of anti-BRAF antibody levels in the sera were examined by enzyme-linked immunosorbent assay (ELISA). The associations between IgA isotype of anti-BRAF antibody levels and the clinical features including age, disease duration and laboratory parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score in 28 joints (DAS28), anti-cyclic citrullinated peptide (anti-CCP) antibody, immunoglobulin and BRAF protein levels in the RA patients were evaluated. Data analyses were performed by using SPSS 19.0 program. RESULTS: The serum IgA isotype of anti-BRAF antibody levels in the RA patients were significantly higher than in the SLE, gout, OA patients and healthy controls, the P value was 0.011, < 0.001, < 0.001 and < 0.001, respectively. The serum IgA isotype of anti-BRAF antibody levels in the SS patients were also significantly higher than in the SLE, gout, OA patients and healthy controls, the P value was 0.029, 0.004, 0.001 and < 0.001, respectively. However, there was no difference between the RA and SS patients (P=0.762). IgA isotype of anti-BRAF antibody was measurable in the RA patients without RF, anti-CCP antibody or anti-keratin antibody (AKA) antibodies. The levels of IgA isotype of anti-BRAF antibody in the RA patients did not show any correlation with clinical features such as age and disease duration or laboratory parameters including ESR, CRP, RF, DAS28, anti-CCP antibody, immunoglobulin and BRAF protein levels. Compared with the clinical features and laboratory indexes of normal and elevated levels of IgA isotype of anti-BRAF antibody groups in the RA patients, there was no significant differences between the two groups in age, disease duration, ESR, CRP, RF, DAS28, anti-CCP antibody, immunoglobulin or BRAF protein levels. CONCLUSION: The elevated level of IgA isotype of anti-BRAF antibody in the RA patients showed that IgA isotype of anti-BRAF antibody might play a role in the pathogenesis of RA. Furthermore, detection of IgA isotype of anti-BRAF antibody in the serum negative RA patients showed that it might be helpful for the diagnosis of the serum negative RA patients.

Unveiling the Enhancement of Spontaneous Emission at Exceptional Points.

Exceptional points (EPs), singularities of non-Hermitian physics where complex spectral resonances degenerate, are one of the most exotic features of nonequilibrium open systems with unique properties. For instance, the emission rate of quantum emitters placed near resonators with EPs is enhanced (compared to the free-space emission rate) by a factor that scales quadratically with the resonance quality factor. Here, we verify the theory of spontaneous emission at EPs by measuring photoluminescence from photonic-crystal slabs that are embedded with a high-quantum-yield active material. While our experimental results verify the theoretically predicted enhancement, they also highlight the practical limitations on the enhancement due to material loss. Our designed structures can be used in applications that require enhanced and controlled emission, such as quantum sensing and imaging.

[Clinical characteristics of patients with rheumatoid arthritis complicated with venous thrombosis of lower extremities].

OBJECTIVE: To analyze the clinical characteristics of patients with rheumatoid arthritis (RA) complicated with venous thrombosis of lower extremities, and to improve the awareness of this condition. METHODS: The clinical and laboratory data of 502 RA patients hospitalized in Department of Rheumatology and Immunology Peking University Third Hospital from November 1, 2013 to December 31, 2020 were collected, retrospective analysis was made on the RA patients who were diagnosed with lower limb vein thrombosis on discharge but hadn't on admission, the patients in this group were defined as thrombosis group, and the other patients without lower limb vein thrombosis were taken as control group. Single factor analysis was conducted between the two groups. Then multivariate Logistic regression analysis was used to analyze the independent risk factors of RA complicated with lower limb venous thrombosis with statistical significance in univariate analysis. RESULTS: There were 34 patients (6.77%) in the thrombosis group and 468 patients (93.23%) in the control group. The age of thrombosis group was 34-86 years (median age was 71 years); 23 were female and 11 were male; there were 20 cases with unilateral lower limb vein thrombosis and 14 cases with bilateral lower limb vein thrombosis; pulmonary embolism in 3 cases (low risk).In the thrombosis group 17 (50.0%) patients were bedridden for more than one week or needed crutches/wheelchairs before admission. 29 cases(85.3%)had large joint involvement of lower extremities, including 22 cases of knee joint involvement, 1 case of hip joint involvement, 2 cases of ankle joint involvement, and 4 cases with both knee and hip joint involvement. In the thrombosis group, the high, middle and low disease activity scores 28(DAS28) were 23 (67.6%), 9 (26.5%) and 2 (5.9%), respectively. There were 21 patients in the thrombosis group had completed thrombosis related examinations, only 4 patients were positive for anti-cardiolipin antibody or anti-ß2 glycoprotein 1 antibody or lupus anticoagulant, the rests were all negative. In the thrombosis group, age and platelet (PLT) level were significantly higher than those in the control group [71 (60, 77) years vs. 60 (51, 68) years, Z=-3.873, P < 0.01, (328.53× 109±119.06 × 109) /L vs.(278.68 × 109±104.50 × 109)/L, t=2.660, P < 0.01, respectively]. The proportion of D-Dimer increased in the thrombosis group as well as the positivity rheumatoid factor (RF) was much higher than those in the control group (94.1% vs.66.4%, χ2=11.192, P < 0.01; 85.3% vs.67.1%, χ2=4.852, P < 0.05, respectively). Multivariate Logistic regression analysis showed that age (OR=1.063, 95%CI: 1.026-1.101, P=0.001), D-Dimer increased (OR=4.968, 95%CI: 1.136-21.730, P=0.033) and PLT level (OR=1.004, 95%CI: 1.001-1.007, P=0.022) were the independent risk factors for RA complica-ted with lower extremity venous thrombosis. CONCLUSION: RA patients have potential risk of thrombosis of lower extremities. For the older age, D-Dimer and PLT elevated, especially those who were bedridden, RF positive and had high disease activity, should be alert to the risk.

[Cross-sectional study on quality of life and disease activity of rheumatoid arthritis patients].

OBJECTIVE: To analyze health related quality of life (HR-QoL) and physical function of outpatient department patients with rheumatoid arthritis (RA), and to analyze disease activity influence in HR-QoL and functional capacity as well as the divergences between different disease activity standards. METHODS: The demographic and clinical data of 207 RA cases from Department of Rheumatology and Immunology, Peking University Third Hospital from Jan 2021 to Jul 2021 were collected. RA-specific quality of life (RA-QoL) and the medical outcome 36-item short form health survey (SF-36)were collected to estimate the quality of life. The t test was used for the quantitative data in accordance with normal distribution. RESULTS: A total of 207 cases were included, with RA-QoL score of 7.8±7.1, physical component summary (PCS) score of 63.8±23.8, and mental component summary (MCS) score of 71.7±21.0. According to disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), there were 119 patients (59.5%) with remission and low disease activity, and 125 patients (62.5%) with simplified disease activity index (SDAI). The HR-QoL of the patients with remission or low disease activity was significantly better than that of the patients with moderate or high disease activity. The physical function (76.7±17.2 vs. 86.4±15.0, t=2.855, P < 0.01), bodily pain (67.8±8.5 vs. 77.7±15.6, t=4.277, P < 0.01) and health transition (52.8±22.3 vs. 63.9±24.1, t=2.134, P < 0.05) in the low disease activity (LDA) group were lower than those in the complete remission (REM) group according to DAS28-ESR. Other domains of SF-36 and RA-QoL had no differences between these two groups. PCS in the LDA group was lower than that in the REM group (68.3±15.2 vs. 77.3±15.2, t=2.716, P < 0.01), but MCS was not different between the two groups. Determined by SDAI, the RA-QoL score in the LDA group was significantly higher than that in the REM group (9.4±7.1 vs. 6.0±4.8, t=-2.260, P < 0.05), the various dimensions of physical function in the SF-36 score and the PCS score (69.9±16.4 vs. 81.4±15.1, t=3.879, P < 0.05) were lower than that in the REM group, and the MCS score was lower than that in the REM group (67.9±19.3 vs. 74.5±18.8, t=2.721, P < 0.01). CONCLUSION: The RA-QoL and SF-36 scores of RA patients in outpatient clinics were better, and the MCS was higher than the PCS. Treat-to-target is essential to improve HR-QoL. SDAI can better indicate the HR-QoL of each domain in REM and LDA RA patients.

[Re-recognition of methotrexate monotherapy in rheumatoid arthritis].

With the in-depth research on treatment drugs of rheumatoid arthritis (RA), a variety of disease modifying anti-rheumatic drugs (DMARDs) have been approved for the treatment of RA. By now methotrexate (MTX) is still the anchor drug for RA treatment. The 2019 European League Against Rheumatism (EULAR) and 2021 American College of Rheumatology (ACR) recommendations for RA management both point out that for newly diagnosed RA patients, MTX monotherapy should be used as the first choice, which shows the importance of MTX monotherapy in DMARDs naïve RA. This paper mainly reviews the relevant researches on MTX in the treatment of RA in recent years, especially the relevant literature on the use of MTX monotherapy in initial treatment of RA. We summarize the development history, efficacy, treatment and adverse reactions of MTX to recognize the importance of MTX in the treatment of RA and the feasibility of MTX monotherapy.

[Analysis of cervical instability and clinical characteristics in treatment-naive rheumatoid arthritis patients].

OBJECTIVE: To study the proportion of cervical spine instability in treatment-naive rheumatoid arthritis (RA) patients, to investigate the associated neck symptoms, and to analyze the clinical characteristics in treatment-naive RA patients and treated RA patients. METHODS: RA patients who underwent cervical spine X-ray imaging from the Department of Rheumatology and Immunology of Peking University Third Hospital and Peking University Shenzhen Hospital from August 2015 to October 2019 and had clinical records of medication administration were included. Clinical and laboratory data including cervical symptoms and X-ray imaging data of cervical spine were collected. The constituent ratio of cervical spine instability in treatment-naive RA patients was statistically analyzed. The clinical data and laboratory data were analyzed by t-test, u-test and chi square to explore the clinical characteristics of the treatment-naive RA patients with cervical instability. RESULTS: Of the 408 RA patients, 105 patients were treatment-naive. Of the 105 treatment-naive patients, 82.9% (87/105) were female, with an average age of (52±14) years, the median duration of the disease was 24 months, the shortest history was 2 weeks, and the longest history was 30 years. 28.6% (30/105) of the treatment-naive RA patients showed cervical spine instability. The prevalence of cervical instability was 13.6% in the treatment-naive RA patients with disease duration less than 24 months. Among them, there were no significant differences in neck symptoms between cervical spine instability group and none cervical spine instability group. The patients with cervical spine instability had a longer duration of disease [60 (18, 180) months vs.16 (8, 51) months], a higher proportion of peripheral joint deformity (63.3%vs.21.3%), and a lower hemoglobin [(106.90±21.61) g/L vs. (115.77±14.69) g/L]. There was no significant difference in the occurrence of cervical instability in the treatment-naive RA patients compared with treated RA patients. Among the RA patients with cervical instability, there was no statistically significant difference in the composition of each type between the patients with treatment-naive RA and patients with treated RA, except for a shorter duration of disease [120.0 (72.0, 240.0) months vs. 60.0 (27.0, 167.5) months]. CONCLUSION: 28.6% of treatment-naive RA patients showed cervical spine instability. Cervical instability was also common in RA patients with a duration less than 24 months. There was no significant correlation between cervical instability and neck symptoms. Patients with cervical spine instability had a long-term disease, a higher proportion of peripheral joint deformity and a lower hemoglobin. Controlling the condition of RA early may help to control the progression of cervical involvement in patients with RA.

[A novel attention fusion network-based multiple instance learning framework to automate diagnosis of chronic gastritis with multiple indicators].

Objective: To explore the performance of the attention-multiple instance learning (MIL) framework, an attention fusion network-based MIL, in the automated diagnosis of chronic gastritis with multiple indicators. Methods: A total of 1 015 biopsy cases of gastritis diagnosed in Fudan University Cancer Hospital, Shanghai, China and 115 biopsy cases of gastritis diagnosed in Shanghai Pudong Hospital, Shanghai, China were collected from January 1st to December 31st in 2018. All pathological sections were digitally converted into whole slide imaging (WSI). The WSI label was based on the corresponding pathological report, including "activity" "atrophy" and "intestinal metaplasia". The WSI were divided into a training set, a single test set, a mixed test set and an independent test set. The accuracy of automated diagnosis for the Attention-MIL model was validated in three test sets. Results: The area under receive-operator curve (AUC) values of Attention-MIL model in single test sets of 240 WSI were: activity 0.98, atrophy 0.89, and intestinal metaplasia 0.98; the average accuracy of the three indicators was 94.2%. The AUC values in mixed test sets of 117 WSI were: activity 0.95, atrophy 0.86, and intestinal metaplasia 0.94; the average accuracy of the three indicators was 88.3%. The AUC values in independent test sets of 115 WSI were: activity 0.93, atrophy 0.84, and intestinal metaplasia 0.90; the average accuracy of the three indicators was 85.5%. Conclusions: To assist in pathological diagnosis of chronic gastritis, the diagnostic accuracy of Attention-MIL model is very close to that of pathologists. Thus, it is suitable for practical application of artificial intelligence technology.

[Clinical and laboratory characteristics of rheumatoid arthritis with positive antinuclear antibody].

OBJECTIVE: To analyse the clinical and laboratory characteristics of antinuclear antibody (ANA) positive rheumatoid arthritis (RA) patients. METHODS: The clinical and laboratory data of 428 RA cases from Department of of Rheumatology and Immunology Peking University Third Hospital from Jan 2013 to Dec 2018 were collected and used to analyse characters between ANA positive group and ANA negative group. T test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. RESULTS: The number of ANA positive group was 231 (54%). The female rate was obviously higher in ANA positive group (82.7% vs. 63.5%, χ2=20.355, P < 0.01). The rate of metatarsophalangeal joints (MTPJs) involvement was lower in ANA positive group (22.1%) than in ANA negative group (33.0) (χ2=6.414, P < 0.05). The incidence of secondary Sjögren's syndrome (sSS) was much higher in ANA positive group(19.5% vs. 4.1%, χ2=23.300, P < 0.01). The positivity of rheumatoid factor (RF), as well as the positivity of anti-cyclic citrullinated peptide(CCP) antibody was much higher in ANA positive group (77.1% vs. 53.8%, χ2=25.743, P < 0.01, 74.9% vs. 59.4%, χ2=11.694, P < 0.01, respectively). The levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) of ANA positive group were higher [(15.1±5.1) g/L vs. (13.8±5.3) g/L, t=2.359, P < 0.05, 1.25 (0.92) g/L vs. 1.05 (0.65) g/L, Z=-3.449, P < 0.01, respectively]. But the levels of hemoglobin (Hb) and platelet (PLT) was lower in ANA positive group[(109.64±17.98) vs. (114.47±18.48) g/L, t=-2.734, P < 0.01; (266.4×109±104.6×109) vs. (295.9×109±100.1×109) /L, t=-2.970, P < 0.01, respectively]. CONCLUSION: The incidence of sSS was obviously higher in ANA positive group than in ANA negative group. Serum IgG of ANA positive group was higher, but Hb and PLT were lower.

[Population distribution and clinical characteristics in rheumatoid arthritis patients with cervical spine instability].

OBJECTIVE: To investigate the population distribution of cervical spine instability in rheumatoid arthritis (RA) patients, and to analyze the clinical characteristics in RA patients with cervical spine instability. METHODS: A total of 439 RA patients who had completed cervical spine X-ray examination from Department of Rheumatology and Immunology of Peking University Shenzhen Hospital and Peking University Third Hospital from August 2015 to March 2019 were enrolled. The clinical data, laboratory data and cervical radiographic data were collected and analyzed by t-test, rank sum test and Chi-square test to clarify the clinical characteristics in the RA patients with cervical spine instability. RESULTS: Of the 439 RA patients, 80.9% (355/439) were female, with an average age of (52.9±13.9) years, a median duration of the disease was 60 months, the shortest history was 2 weeks, and the longest history was up to 46 years. 29.6% (130/439) of the RA patients showed cervical spine instability. Among them, 20 RA patients were complicated with two different types of cervical instability, the atlantoaxial subluxation (AAS) accounted for 24.6% (108/439), the vertical subluxation (VS) accounted for 7.3% (32/439) and the subluxial subluxations (SAS) accounted for 2.3% (10/439). The patients with cervical spine instability had a longer duration of disease [120 (36, 240) months vs. 48 (12, 120) months], a higher proportion of peripheral joint deformity (56.9% vs. 29.9%), and a higher visual analog scale (VAS) measuring general health score (4.89±2.49 vs. 3.93±2.38), a lower hemoglobin [(111.31±19.44) g/L vs. (115.56±16.60) g/L] and a higher positive rate of anti-cyclic citrullina-ted peptide (CCP) antibody (90.8% vs. 76.6%). There were no significant differences in gender, age, number of swollen joints, number of tenderness joints, erythrocyte sedimentation rate, rheumatoid factor level, 28-joint disease activity score, positive rate of anti keratin antibody, duration of glucocorticoid use and duration of disease modifying anti-rheumatic drugs use between the two groups. CONCLUSION: In the study, 29.6% of the RA patients showed cervical spine instability. RA patients with cervical spine instability had a long-term disease, a higher proportion of peripheral joint deformity, a higher VAS measuring general health score, a lower hemoglobin and a higher positive rate of anti-CCP antibody.

[Effect of risperidone on prepulse inhibition of the startle reflex and P50 deficit in patients with first-episode and chronic schizophrenia].

Objective: To investigate the effect of antipsychotic medicine risperidone on prepulse inhibition of the startle reflex (PPI) and P50 deficit in patients with first-episode and chronic. Methods: Thirty-eight patients with first-episode schizophrenia and 36 patients with chronic schizophrenia, both in acute stage, were enrolled in the study. All patients were treated with risperidone of different doses (2 to 6mg/d). All patients fulfilled the evaluation of PPI and P50 before treatment and 8 weeks after treatment. The psychotic symptoms were assessed with Positive and Negative Syndrome Scale (PANSS), and the therapeutic effects were evaluated with PANSS reduction rate. Results: (1) There was no significant difference in PPI and P50 parameters between the two groups before treatment (PPI ratio: first group 43%±29%, chronic group 42%±27%, P>0.05; P50 S2/S1 ratio: first group 83%±33%, chronic group 82%±24%, P>0.05). (2) There was no significant correlation between PPI and P50 inhibition parameters and disease course, psychotic episodes and psychiatric symptoms (PANSS total score, positive symptoms score, negative symptoms score and general psychopathology symptoms score) of schizophrenia (P>0.05). (3) Except the group main effect for S2 amplitude (F=5.75, P=0.019), there was no significant change for main effect and interaction of the other P50 and PPI inhibition ratio parameters after treatment (P50 S2/S1 ratio: first group before treatment 83%±33%, after treatment 85%±49%, P>0.05; chronic group before treatment 82%±44%, after treatment 84%±35%, P>0.05. PPI ratio: first group before treatment 43%±29%, after treatment 42%±27%; chronic group before treatment 42%±27%, after treatment 41%±28%,P>0.05). The effect of risperidone on P50 and PPI parameters was not related to the therapeutic effect. Conclusion: Deficit in sensory gating inhibition exists in both first-episode schizophrenia and chronic schizophrenia, and risperidone is not effective in treating the deficit in sensory gating (PPI and P50) inhibition of schizophrenia.

[Clinical characteristics of elderly and younger onset rheumatoid arthritis].

Objective: To compare the clinical and laboratory characteristics and therapy methods of elderly onset rheumatoid arthritis (EORA) and younger onset rheumatoid arthritis (YORA). Methods: The clinical, laboratory and therapeutic data of 481 RA patients in the Department of Rheumatology and Immunology in Peking University Third Hospital from January 2013 to December 2018 were collected and used to analyze the difference of characteristics between EORA group and YORA group, which might be useful for better diagnosis and treatment of EORA patients. Quantitative data of normal distribution were compared with t test between the two groups. Results: There were 481 patients in this cohort, of which 137(28.5%) were EORA, 344(71.5%) were YORA, with a mean age of (59±14) years (19-87 years). There were 358 females (74.4%) and 123 males (25.6%). The percentage of male patients was obviously higher in EORA group (36.5% vs 21.2%, χ(2)=12.012, P<0.01), and the average disease course was obviously shorter (Z=-7.985, P<0.01). Disease Activity Score 28 (DAS28) score was higher in EORA group (5.6±1.3 vs 5.2±1.6, t=2.549, P<0.05), meanwhile the incidences of pleural effusion and interstitial lung disease (ILD) were higher (6.6% vs 1.7%, 29.9% vs 18.3%, respectively; χ(2)=7.550, 7.797, both P<0.05). The incidences of venous thrombosis, primary hypertension, diabetes mellitus, cerebrovascular disease, coronary heart disease (CHD), peripheral atherosclerosis and cataract in EORA group were all significantly higher than those in YORA group (all P<0.05). Erythrocyte sedimentation rate (ESR) and D-Dimer in EORA group were all remarkably higher (both P<0.05). The rate of using glucocorticoid in EORA group was higher but the rate of using methotrexate and anti-tumor necrosis factor-α agents were lower (χ(2)=5.271, 8.407, 9.356, all P<0.05). Conclusion: Compared to YORA group, the percentage of male patients and disease activity of EORA group are higher. The occurrence of pleural effusion, ILD, venous thrombosis, primary hypertension, diabetes mellitus, cerebrovascular disease, CHD, peripheral atherosclerosis and cataract in EORA group are higher than those in YORA group.

Function of IL-33 in Wound Age Estimation of Skin Wounds in Mice.

ABSTRACT: Objective To explore the application value of interleukin-33 （IL-33） in wound age estimation in forensic practice by observing the sequential changes of IL-33 after skin wound. Methods Skin wound models were generated on the back of mice with a round file of 5 mm in diameter. Skin samples of the same size were taken from the same parts of mice in control group and injury group 1 h, 3 h, 6 h, 12 h, 1 d, 3 d, 5 d, 7 d and 10 d after skin wound. Hematoxylin-eosin （HE） staining method was applied to observe the morphological changes in the recovering process after skin wound. Western blotting, immunohistochemistry staining and double immunofluorescence staining methods were applied to detect the expression changes of IL-33 in the skin wound samples. Results The results of Western blotting showed that the expression of IL-33 protein decreased slightly at 3 h after skin wound, increased gradually at 6 h after skin wound, and reached the peak value at 3 d, then decreased gradually. Immunohistochemistry staining results showed that faint positive expression of IL-33 was observed in epidermis, hair follicles, sebaceous glands and dermal resident cells of the control group skin. The positive cell rate of IL-33 increased at 3 h after skin wound and reached the peak value at 3 d, then decreased gradually. The results of double immunofluorescence staining showed that the majority of IL-33 positive cells from 1 d to 3 d after wound were macrophages, while the majority of IL-33 positive cells from 5 d to 7 d after wound were myofibroblasts. In addition, the results of HE staining showed that the wound healing process of the skin wound model was consistent with the pathological development law of inflammation. Conclusion IL-33 could become a reference index for wound age estimation of skin wound in forensic practice.

Application of Virtual Anatomy Technology in Postmortem Examination of Medical Dispute Cases.

ABSTRACT: Objective To discuss the application value of CT scanning technology in cause of death determination of medical dispute cases. Methods From July 2017 to December 2018, postmortem CT imaging data of 12 medical dispute cases were collected. CT imaging diagnosis results and anatomy findings as well as differences between antemortem and postmortem CT diagnosis were compared. The advantages and disadvantages of CT routine tests of the cadavers in terms of the diagnosis of disease and damage were analyzed. Results The comparison between CT imaging diagnosis and anatomical findings showed that CT scans had advantages in the diagnosis of disease and damage with large differences in density changes, such as atelectasis, pneumonia, calcification, fracture and hemorrhage, etc. The comparison of CT diagnosis in antemortem and postmortem examination showed that the cadavers of medical dispute cases were well preserved and that postmortem CT scan was meaningful for the diagnosis of antemortem diseases. Conclusion Virtual anatomy technology has a relatively high application value in postmortem examination of medical dispute cases. It can provide effective information for the appraisers before the autopsy and can also provide a reference for cause of death analysis when the anatomy cannot be performed.

[Clinical characteristics of psoriatic arthritis with positive rheumatoid factor or anti-cyclic citrullinated peptide antibody].

OBJECTIVE: To analyze the clinical and laboratory features of psoriatic arthritis (PsA) patients with positive rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibody. METHODS: In the study, 77 PsA patients who were hospitalized in the Department of Rheumatology and Immunology of Peking University Third Hospital from January 2007 to June 2019 were enrolled. All the patients met Classification Criteria for Psoriatic Arthritis or Moll or Wright Criteria. Rheumatoid factor (RF) and anti-cyclic-citrullinated peptide (CCP) antibody were tested in these patients. According to whether anti-CCP antibody or RF was detected in serum, all the patients were divided into anti-CCP antibody or RF positive group (15 cases), anti-CCP antibody or RF negative group (62 cases). According to the detection of anti-CCP antibody in serum, all the patients were divided into anti-CCP antibody positive group (7 cases) and anti-CCP antibody negative group (70 cases). Clinical and laboratory data were collected. The differences of clinical and laboratory indicators between the RF or anti-CCP antibody positive and negative PsA patients were compared. Clinical and laboratory indicators between the anti-CCP antibody positive and negative patients were also compared. RESULTS: Among the 77 patients, 15 were RF or anti-CCP antibody positive, of whom 8 were only RF positive and 2 were only anti-CCP antibody positive, and both of RF and anti-CCP antibody were positive in 5 cases. The RF or anti-CCP antibody positive PsA patients were older than those in the negative group [(58.2±14.8) years vs. (46.69±12.27) years, P=0.002]. And metacarpophalangeal joints, elbow joints and shoulder joints were more likely to be involved in RF or anti-CCP antibody positive PsA patients. PsA patients in the anti-CCP antibody positive group were older than those in the negative group [(62.43±14.34) years vs. (47.59±12.75) years old, P=0.005]. The positive rate of RF and serum level of fibrinogen in the anti-CCP antibody positive group were higher than those in the negative group. The PsA patients in the anti-CCP antibody positive group were all polyarthritis, while 68.6% patients in the negative group were polyarthritis, but there was no statistical difference between the two groups. There was no statistical difference in sausage fingers/toes, changes in nails and enthesitis, and bone erosion on radiographs between the RF or anti-CCP antibody positive and negative PsA patients. There was also no statistical difference in sausage fingers/toes, bone erosion on radiographs, and changes in nails and enthesitis between the anti-CCP antibody positive and negative patients. CONCLUSION: RF and anti-CCP antibodies can be detected in the serum of some PsA patients. RF or anti-CCP antibody positive PsA patients were older than those in negative PsA patients. Metacarpophalangeal joints, elbow joints and shoulder joints were more likely to be involved in RF or anti-CCP antibody positive PsA patients. Anti-CCP antibody positive PsA patients were older and had higher levels of RF positive rate and fibrinogen level.

[Clinical characteristics and treatment outcomes of macrophage activation syndrome in adults: A case series of 67 patients].

OBJECTIVE: To described the clinical and laboratory features and outcome of 67 macrophage activation syndrome (MAS). METHODS: A total of 67 MAS patients from three centers from January 2007 to December 2017 were enrolled. Clinical and laboratory features, and response to therapy were analyzed. Predictive factors for remission and survival were explored. RESULTS: We identified a mean age of (36.1±16.3) years at diagnosis of MAS and a median connective tissue disease (CTD) duration of 8 months prior to MAS development. Among 67 MAS patients identified, underlying diseases included adult-onset Still's disease (AOSD) in 56.7% and systemic lupus erythematosus (SLE) in 30.0%. Fever and splenomegaly were found in 100.0% and 82.1% of the patients, respectively. Ferritinemia and elevation of serum soluble interleukin-2 receptor was seen in 100.0% and 93.2% of the patients. Serum levels of alanine aminotransferase, D-dimer, ferritin and C reactive protein were significantly higher in MAS associated with the AOSD patients than in MAS associated with the SLE patients. A significant decrease of erythrocyte sedimentation rate was found in MAS associated with AOSD, as compared with MAS associated with SLE. The most commonly used therapy was corticosteroids, which were initially administered in 100.0% of the patients. Intravenous immunoglobulin (IVIG) was administered in 91.0%, cyclosporine A in 64.2%, and etoposide in 46.3% of the patients, respectively. The induction therapy yielded a complete remission (CR) at the end of week 8 in 47.8% of the MAS patients. The overall mortality rate at the end of week 16 was 22.4%. The median serum levels of gamma-glutamyltransferase, alkaline phosphatase, total bilirubin and direct bilirubin were significantly lower in the patients who achieved complete remission at the end of week 8 than in those who did not, and splenomegaly was significantly less frequent (71.9% vs.91.4%, P=0.037). Both the mean age at diagnosis of MAS and the mean age at diagnosis of underlying CTD of the deceased patients were elder than those of the survived population (P=0.014 and P=0.017, respectively). The platelet count was significantly less in the deceased population as compared with the living population (P=0.018). No addition of cyclosporine A (P=0.004) was identified as risk factors associated with death in Logistic regression analysis. CONCLUSION: MAS secondary to connective tissue disease is most common with AOSD and SLE. In terms of laboratory findings, there were considerable differences between the patients with underlying SLE and those with AOSD. Advanced age and low platelet counts are significant predictive factors for death, while treatment with cyclosporine may reduce the risk.

[The dosimetry comparison study between 3D print template and free-hand guided of precision (125)I seeds implantation on superficial metastatic carcinoma].

Objective: To compare the dose difference of (125)I seeds implantation on superficial metastatic carcinoma between 3D print template guided operation and traditional implantation. To investigate the accuracy of seeds implantation according preplan guided by 3D print template. Methods: A total of 21 cases of patient with 27 lesions underwent (125)I seeds implantation from January 2015 to May 2018 in Hebei General Hospital were analyzed retrospectively. In which, ten lesions underwent seeds implantation guided by 3D print template (template group) and 17 lesions underwent free-hand traditional implantation (traditional group). All patients had been fixed as the position of operation and then performed CT scan. After preplan was designed, the 3D templates were printed in template group. Postplan was performed after the operation.The dose volume histogram, D90 was calculated. The D90 pre and post operation were collected and compared in each group. The difference of D90 and the percentage difference of D90 between pre and post operation were calculated by the formula D90d=D90post-D90pre, D90d%=(D90post-D90pre)/D90pre×100%, and compared the difference between two groups. Results: The mean D90 pre and post operation in template group were (92±26) and (93±27) Gy respectively, t=-0.749, P=0.473. The mean D90 pre and post operation in traditional group were (104±29) and (104±26) Gy respectively, t=-0.139, P=0.891. The difference of D90 in two groups were (3.1±2.4) and (10.0±8.7) Gy, Z=-2.5, P=0.012. The percentage difference of D90 in two groups were 3.1%±1.9% and 9.5%±7.9%, Compared with the traditional group, the template group had smaller fluctuations, and the difference was statistically significant (Z=-2.7, P=0.006) (all P<0.05). Conclusions: The dose parameters of 3D template guided seeds implantation between postplan and preplan are nearly consistent.3D template has good repeatability, which provides a theoretical basis for the popularization of 3D printing technology.

Expression of Annexin A1 during Skin Incised Wound Healing in Mice.

OBJECTIVES: To investigate the expression changes of annexin A1 （ANXA1） during the process of skin incision healing, and to explore its expression and function during skin injury repair. METHODS: The skin injury model of mice was prepared, and skin tissues of the controls and the injured group at 6 h, 12 h, 1 d, 3 d, 5 d, 7 d, 10 d and 14 d after injuries were taken. The morphological changes of the wound were observed by hematoxylin-eosin （HE） staining, and the expression of ANXA1 was detected by immunohistochemistry （IHC） and Western blotting. RESULTS: HE staining showed normal healing of skin wounds. IHC results revealed that ANXA1 was expressed in the epidermis, hair follicle, sebaceous gland and vascular endothelium. In the injured group, the expression of ANXA1 was enhanced in epidermis and skin appendages around the wound 6-12 h after injury, and ANXA1 was also highly expressed in neutrophils and a small number of mononuclear cells. ANXA1 was mainly positively expressed in monocytes, neovascular endothelial cells and fibroblasts, and small amount of fibroblasts at 1-3 d, 5-10 d, and 14 d after injury, respectively. Western blotting showed that, compared with the controls, the expression of ANXA1 was significantly increased at 6 h after injury, peaked at 1 d, and then decreased gradually in the injured group. CONCLUSIONS: ANXA1 may be involved in the regulation of skin damage repair, with time-dependent expression during skin wound healing, and thus is expected to be a biological marker for inferring the wound formation time.

Time-dependent Expression and Distribution of AChE during the Skin Incised Wound Healing in Mice.

ABSTRACT: Objective To study the time-dependent expression and distribution of acetylcholinesterase （AChE） during skin incised wound healing in mice, and discuss its effect in wound healing as well as the feasibility of using it as a reference index for wound age estimation. Methods A total of 45 C57BL/KsJ mice were randomly divided into one control group and eight incised groups. The skin incised wound model was established in the incised groups with samples of skin wounds taken at 6 h, 12 h, 1 d, 3 d, 5 d, 7 d, 10 d and 14 d post-injury respectively, while the uninjured skin tissue was extracted in the control group. Expression and distribution of AChE in skin samples were detected by immunohistochemistry, double immunofluorescence and Western blotting. Results Immunohistochemistry results indicated that AChE was mainly detected in infiltrating polymorphonuclear cells （PMNs） 6 to 12 h post-injury. A large number of AChE-positive mononuclear cells （MNCs） were observed 1 to 3 d post-injury. The AChE-positive cells were mainly fibroblastic cells （FBCs） 5 to 14 d post-injury. The ratio of the AChE-positive cells increased initially 6 h post-injury, and reached the peak at 1 d post-injury. Double immunofluorescent staining showed that the majority of AChE-positive MNCs and FBCs expressed macrophage marker and myofibroblast marker, respectively. Western blotting results showed that the relative expression level of AChE in the incised group was higher than that in the control group averagely, reached the peak at 1 d post-injury, then reached a second peak at 7 d post-injury. Conclusion The expression of AChE is found in PMNs, macrophages and myofibroblast during skin wound healing, which indicates it might be involved in the adjustment of inflammatory response and fibrotic repair after injury. Moreover, combined use of various methods for the detection of the expression of AChE would provide reference for skin wound age estimation.